Applications of HPLC-MALDI-TOF MS/MS Phosphoproteomic Analysis in Oncological Clinical Diagnostics

Courtney      L. Haddock; Barry      Holtz; Neil      Senzer; John      Nemunaitis

Abstract

Recent developments in mass spectrometry have brought clinical proteomics to the forefront of cancer diagnosis and treatment, offering reliable, robust and efficient analysis methods for biomarker discovery and monitoring. Proteins control cellular processes through intricate signaling cascades and protein function is often determined by posttranslational modifications. However, alteration of post-translational modifications that control normal cellular processes, such as differentiation, proliferation and apoptosis, has been significantly related to tumorigenesis. Aberrations in protein phosphorylation, for example, offer promising opportunity for disease diagnosis and prognosis and could also serve as a therapeutic indicator for cancer treatment. Recent studies have identified biomarkers involving several cancer types using high-performance liquid chromatography separation and enrichment techniques coupled with matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry for protein identification and quantification. However the clinical implementation of proteomic technologies is not without shortcomings and is still dependent on laboratory research to expand identification of relevant biomarkers.

Keywords: Clinical proteomics, mass spectrometry, phosphoproteome, protein biomarker, Adenosine tri-phosphate, Collision induced dissociation, Epidermal growth factor, Estrogen receptor, Electrospray ionization, Heat shock protein 27, Isotope coded affinity tags, Immobilized metal affinity chromatography